title: Amelioration of Muc5b mucin hypersecretion is enhanced by IL-33 after 2-APB administration in a murine model of allergic rhinitis.
abstract: We attempted to clarify whether hypersecretion of Muc5b mucin from mouse nasal submucosal glands that is enhanced by interleukin (IL)-33 under allergic conditions can be ameliorated by administration of 2-APB. Immunohistochemistry was used to examine both the distribution of T cells in the nasal mucosa of an allergic rhinitis mouse model and expressions of IL-33 receptor ST2 and Muc5b protein in mouse submucosal gland cells. The amounts of protein and mRNA of Orai1, Muc5b, IL-4, IL-5, IL-13 and IL-33 in mouse nasal lavage fluid (NLF) and nasal mucosa were determined using enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction. Expressions of Orai1, Muc5b, IL-4, IL-5, IL-13 and IL-33 were up-regulated in the allergic state and IL-33 increased the levels of Muc5b, IL-4, IL-5 and IL-13, but did not influence proliferation of T cells; however, ST2 was diminished in nasal submucosal gland cells. 2-APB reduced proliferation of T cells and the Orai1 level in the nasal mucosa. It also reduced the concentrations of IL-4, IL-5 and IL-13 in NLF and nasal mucosa, and hypersecretion of Muc5b from glandular cells that was enhanced by IL-33, but did not affect IL-33 production. 2-APB decreased Muc5b mucin hypersecretion from submucosal gland that was enhanced by IL-33 in allergic mice by limiting Ca(2+) release-activated Ca(2+) channel activity in which Orai1 plays a crucial role in the gland cells and/or by controlling channel activation in T cells and proliferation of these cells.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University , P.R. China.
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: W
authors.initials: W
authors.lastname: Yan
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: S
authors.initials: S
authors.lastname: Liang
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage*; D015220:Calcium Channels / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D000067596:Interleukin-33; D007378:Interleukins / Q000008:administration & dosage*; D015640:Ion Channel Gating / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D055257:Mucin-5B / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D000071740:ORAI1 Protein; D065631:Rhinitis, Allergic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D001896:Boron Compounds; D015220:Calcium Channels; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; C524579:Muc5b protein, mouse; D055257:Mucin-5B; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C109986:2-aminoethoxydiphenyl borate